NHPI-catalyzed electrochemical C-H alkylation of indoles with alcohols to access di(indolyl)methanes via radical coupling

Di(indolyl)methanes are widely prevalent in pharmaceuticals, agrochemicals, alkaloids, and natural products. Herein, we report a metal-free method for the uniform synthesis of symmetrical and unsymmetrical 3,3 '-DIMs through N-hydroxyphthalimide (NHPI)-catalyzed electrolytic C-H alkylation of indoles via a radical cross-coupling pathway. This simple and practical protocol provides a route to a host of 3,3 '-DIMs from indoles and alcohols using water as the sole solvent and without metal contamination. Mechanistic studies suggested that the alcohol substrate was oxidized to a carbon radical via a hydrogen atom transfer (HAT) process jointly mediated by NHPI and the anode oxidation process. Importantly, the present indirect electrochemically mediated radical protocol outperforms the traditional Friedel-Crafts route with a broad substrate scope and functional group tolerance, as well as facile gram-scale synthesis without metal contamination.

Automated summary

A metal-free method for the synthesis of symmetrical and unsymmetrical 3,3'-DIMs through electrolytic C-H alkylation of indoles has been reported. The method utilizes N-hydroxyphthalimide as a catalyst and water as the solvent, without any metal contamination.